Ribonomic dissection of LRb-expressing cells and neurons

描述（由申请人提供）：瘦素是一种脂肪细胞衍生的激素，其通过结合和激活瘦素受体（LRb）的特异性“长”同种型向下丘脑发出身体能量储存状态的信号，所述瘦素受体（LRb）在下丘脑神经元的子集中高度表达。以这种方式，足够的瘦素水平信号能量饱足，并用于抑制食欲和允许能量昂贵的神经内分泌功能，如高代谢率，生殖和生长。虽然LRb表达神经元的基因组学对于理解瘦素调节的生理学和识别潜在的治疗靶点具有极大的兴趣，但只有一小部分下丘脑神经元表达LRb并且是瘦素敏感的。因此，用于基因组分析的下丘脑神经元的混合群体内的LRb表达细胞的解剖学和/或功能解剖是有问题的。该提案概述了一种新的方法，用于分离mRNA的细胞类型特异性的方式和开发的细胞模型的瘦素反应。这将使得能够鉴定仅在LRb表达细胞中表达的基因，并分析这些细胞中受激素和/或营养调节的基因。通过这一过程，我们将能够产生一个治疗肥胖和其他神经内分泌疾病的潜在治疗靶点列表。

DESCRIPTION (provided by applicant): Leptin is an adipocyte-derived hormone that signals the status of body energy stores to the hypothalamus by binding and activating a specific "long" isoform of the leptin receptor (LRb) that is highly expressed in a subset of hypothalamic neurons. In this manner, adequate leptin levels signal energy repletion and serve to repress appetite and permit energy-expensive neuroendocrine functions, such as high metabolic rate, reproduction, and growth. While the genomics of LRb-expressing neurons are of great interest for the understanding of leptin-regulated physiology and for the identification of potential therapeutic targets, only a small percentage of hypothalamic neurons express LRb and are leptin-sensitive. Thus, the anatomic and/or functional dissection of LRb-expressing cells within the mixed population of hypothalamic neurons for genomic analysis is problematic. This proposal outlines a novel approach for isolating mRNA in a cell-type specific manner and development of a cellular model of leptin responsiveness. This will enable the identification of genes expressed only in LRb-expressing cells and the analysis of genes subject to hormonal and\or nutrient regulation in these cells. Through this process we will be able to generate a list of potential therapeutic targets for treatment of obesity and other neuroendocrine disorders.